Catheter system having sealing system for preventing back-flow within cerebral vessels

Abstract

Catheter systems for treatment of chronic subdural hematoma (CSDH) are described. The catheter systems are configured to enable passage through small and tortuous vessels within the vasculature and include a sealing system that engages within a vessel that prevent back-flow of polymer agents within vessels when delivering polymer agents to affected vessels. The systems are pre-manufactured as kits to facilitate clinical use and to enable use of a stabilizer catheter (SC) during a procedure.

Description

CATHETER SYSTEM HAVING SEALING SYSTEM FOR PREVENTING BACKFLOW WITHIN CEREBRAL VESSELSFIELD

[0001] Catheter systems for treatment of chronic subdural hematoma (CSDH) are described. The catheter systems include a sealing system that engages within a vessel that prevent back-flow of polymer agents within the vessels when delivering polymer agents to affected vessels. The systems are pre-manufactured as kits to facilitate clinical use and to enable use of a stabilizer catheter (SC) during a procedure.BACKGROUND

[0002] Chronic subdural hematoma (CSDH) is a common neurosurgical condition characterized as an old clot of blood on the surface of the brain beneath the outer covering. These clots most often occur in patients over the age of 60 who have brain atrophy from shrinking or wasting of brain tissue due to age or disease. When the brain shrinks over time within the skull, it has been traditionally understood that minor head trauma can cause tearing of blood vessels over the brain’s surfaces, resulting in a slow accumulation of blood. In an atrophied brain, the clots can become quite large before symptoms occur. Many patients cannot recall any particular traumatic event that may have caused the CSDH.

[0003] The incidence of CSDH has been reported as between 1.72 to 20.6 per 100,000 persons per year. The incidence increases progressively with age and is increased by a factor of 3.5 over the age of 70 and 6.5 over the age of 80.

[0004] The most common complaint is headache but also includes lethargy, memory impairment, confusion, weakness, nausea, vomiting, impaired vision and seizures.

[0005] CSDH is diagnosed via CT and MRI scans.

[0006] Current standards of care include surgically draining the CSDH. This can include drilling a hole in the skull (burr hole) or a craniotomy and the draining the blood mass through a catheter.

[0007] Unfortunately, the clinical course from this treatment is frequently complicated by recurrence with rates reported from 7.5% - 29%. More than 90% of these recurrences happen within two months of primary surgery and often lead to prolonged hospital stays and devastating outcomes in the elderly and frail population that is affected by CSDH. The treatment cost for recurrent CSDH is 132% higher than the treatment for non-recurrent CSDH.Chronic inflammation as the key driver for CSDH

[0008] As noted above, the traditional theory was that head trauma leads to the disruption of bridging veins (acute SDH). Some of these acute hematomas were thought to persist and become CSDH.

[0009] However, recently it has become evident that an inflammatory response of the dural layers from trauma results in formation of new blood vessels (NBVs) with weak vessel walls that are prone to bleed recurrently and thereby cause CSDH. These new vessels mostly arise from one artery that is supplying the meningeal layers of the brain namely the middle meningeal artery as shown in Figure 1.SUMMARY

[0010] In accordance with the disclosure, an assembly is described comprising: a microcatheter (MC) body having a distal catheter tip, the microcatheter body configured with an anti-reflux sealing system adjacent a microcatheter tip, configured to enable contact with a vessel wall to effect sealing of distal fluids from proximal fluids on opposite sides of the sealing system and wherein the sealing system has sufficient compressibility to enable flexure of the sealing system around a tight bend of a patient’s vasculature and to enable passage of an embolizing agent through the microcatheter body from the distal microcatheter tip, the sealing system having a sealing system outer diameter and the microcatheter body having an MC proximal connector; and, a stabilizer catheter (SC) having a SC proximal connector, the SC pre-configured over the microcatheter body between the sealing system and MC proximal connector, the SC having an outer diameter equal to or less than the sealing system outer diameter.

[0011] In various embodiments, the assembly includes:• a valve configured to the assembly between the SC proximal connector and the MC proximal connector and wherein the valve is configured to connect to the SC proximal connector.• a second valve configured to the assembly over the SC and distal to the SC proximal connector.• the SC is 110-125 cm and the MMAC is 145-165 cm.• the MC body includes a first stopper configured to an outer surface of the MC body and the valve is configured with a second stopper and where the first and second stoppers are engageable to limit proximal movement of the MC body relative to the SC.the first and second stoppers are configured to prevent the sealing system from engaging with a distal tip of the SC.• the first stopper is a circumferential disk.• the MC body includes a first stopper configured to an outer surface of the MC body and the SC includes a second stopper configured to an inner surface of the SC and where the first and second stoppers are engageable to limit proximal movement of the MC body relative to the SC.

[0012] In another aspect, a method of manufacturing a microcatheter assembly is described comprising the steps of: forming a MMAC body having a sealing system on a distal tip of the MMAC body and a MMAC proximal end fitting; forming an SC body with a SC proximal end fitting; wherein the MMAC body is configured within the SC body, and wherein the SC body and SC proximal end fitting are configured between the MMAC proximal end fitting and sealing system; and, packaging the assembly.

[0013] In various embodiments:• the method further comprises the step of configuring a valve over the MMAC body distally to the proximal end of the MMAC body.• the method includes the step of configuring a second valve over the SC body distally to the SC end fitting.• the method includes the step of forming a stopper system on the MMAC body and valve.

[0014] In another aspect, a microcatheter is described, the microcatheter comprising: a microcatheter body having a distal catheter tip for placement within a middle meningeal artery (MMA), the catheter body configured with an anti-reflux sealing system adjacent a microcatheter tip, the sealing system being non-inflatable and configured to enable contact with an MMA vessel wall to effect sealing of distal fluids from proximal fluids on opposite sides of the sealing system and wherein the sealing system has sufficient compressibility to enable flexure of the sealing system around a tight bend of a patient’s vasculature and to enable passage of an embolizing agent through the microcatheter body and from the distal microcatheter tip.

[0015] In various embodiments:• the sealing system includes at least one proximally angled disk.• the sealing system has an outer diameter of 0.8-2 mm.• the microcatheter body has an outer diameter of 0.5- 1 .0 mm.• the sealing system is 0-50 mm from the distal microcatheter tip.• the sealing system is 0-5 mm from the distal microcatheter tip.• The outer diameter of the sealing system is 1.5-2.5 times the OD of the microcatheter body.• the sealing system has a softness to minimize vasospasm when contacting a vessel wall.• the microcatheter has a proximal microcatheter section between the sealing system and a proximal end of the microcatheter and distal microcatheter section distal to the proximal microcatheter section and the distal microcatheter section is configured with a distal stiffness less than a proximal microcatheter section stiffness and wherein the distal stiffness facilitates movement of the distal microcatheter section past an MMA bifurcation or MM A tortuous section.

[0016] In another aspect, a kit is described, the kit comprising at least two MMA microcatheters as described wherein each MMA catheter has a sealing system having a different outside diameter.DESCRIPTION OF THE DRAWINGS

[0017] Aspects of the disclosure are described with reference to the drawings in which:Figure 1 is a schematic diagram of the middle meningeal artery (MMA) or equivalent artery with its branches.Figure 2 is a schematic diagram of CSDH and two common surgical options including burr hole (A) and craniotomy (B).Figure 3 is a schematic diagram of middle meningeal artery (MMA) embolization showing (A) Chronic subdural hematoma, CSDH, with MMA supplying the covering of the brain and giving rise to many newly formed, curvy vessels (NBVs) with weak vessel walls that recurrently bleed and give rise to the CSDH. (B) shows a catheter delivering the embolic agents into the vessel. (C) shows, after few weeks, how the embolization, the pathological curvy vessels have diminished.Figure 3A is a schematic diagram showing the delivery of an embolic agent in accordance with the prior art.Figure 3B is a schematic diagram showing the delivery of an embolic agent through a catheter having a detachable tip in accordance with the prior art.Figure 3C is a schematic diagram showing how a microcatheter may become stuck at vessel bifurcation.Figure 4 is a schematic diagram of an MMA catheter in accordance with the present disclosure.Figure 4A is a schematic diagram of a bulb sealing system in accordance with one embodiment of the present disclosure having circumferential grooves.Figure 4B is a schematic diagram of a bulb sealing system in accordance with one embodiment of the present disclosure having a helical groove.Figure 4C is a schematic diagram of a bulb sealing system in accordance with one embodiment of the present disclosure having a truncated bulb and helical groove.Figure 4D is a schematic diagram of a bulb sealing system in accordance with one embodiment of the present disclosure having a truncated bulb and circumferential grooves.Figure 5 is a schematic diagram of an MMA catheter positioned within a tortuous vessel.Figure 6 is a schematic diagram of an MMA catheter having a sealing disks sealing system.Figures 6A-6C are schematic diagrams of an MMA catheter having an invertible conical leaf sealing system where 6A shows the MMA catheter being advanced, 6B shows the step of inverting the conical leaf and 6C shows the conical leaf expanding against the vessel with the introduction of polymer into a vessel.Figure 7A is a schematic diagram of a section of an MMA artery with a bifurcation showing a mechanism of how a microcatheter can get stuck as it is being advanced.Figures 7B and 7C are schematic diagrams of an embodiment of a microcatheter having a disk sealing system with a tapered distal edge in accordance with one embodiment of the disclosure.Figure 8 is a schematic diagram of a distal region of a microcatheter system configured with a stabilizer catheter and a guide catheter.Figure 8A is a schematic diagram of a distal and proximal region of an MMA microcatheter system configured with a stabilizer catheter, guide catheter and microwire that has been assembled in preparation for a procedure.Figure 8B is a schematic diagram of a proximal region of an assembled microcatheter kit system configured with a stabilizer catheter.Figures 8C and 8D are schematic diagrams of an integrated stopper system configured to limit movement of a MMA catheter relative to a stabilizer catheter in accordance with various embodiments.DESCRIPTION

[0018] The inventors who have skill and experience in endovascular surgery have recognized problems in the treatment of CSDH and have developed catheter systems designed to improve the treatment of CSDH.Surgical treatment

[0019] Currently, surgical drainage remains the mainstay of treatment for symptomatic CSDH. As shown in Figure 2, CSDHs are commonly treated with burr hole 20 or craniotomy 22 surgery to enable drainage of the hematoma via a catheter. Surgical drainage is considered relatively straightforward. However, despite surgical treatment, many CSDH reoccur, with recurrence rates ranging between 7.5% - 29%.

[0020] Importantly, surgery does not tackle any underlying inflammatory changes, and is therefore only a symptomatic treatment, and does not eliminate the cause of CSDH namely any underlying chronic inflammation. Surgery also often necessitates antiplatelet or anticoagulant therapy to avoid perioperative complications. As is known, the use of these agents further increases the risk of hematoma recurrence. Thus, surgical treatment is problematic in that it does not truly address the underlying cause of the CSDH.

[0021] Within this description reference is made to the middle meningeal artery (MMA) as a location of treatment for CSDH. However, it is understood that treatments in some cases may be affected in related or nearby vessels depending on a particular situation. Thus, the term “equivalent vessel” is a vessel that is substantially at the same anatomical level as the MMA in which CSDH treatment may affected. Generally, when the term MMA is mentioned, it includes any equivalent vessel.

[0022] Within this description, reference is made to various catheters. For the purposes of general description, it is understood that a microcatheter is a catheter generally in the range of 1-3 French (0.3-1 mm) and has the general characteristics of a microcatheter (MC) as known to those skilled in the art. Generally, a MC has the ability to ride over a microwire that has been placed within a vessel and that can be pushed into a vessel having a diameter modestly larger than the outer diameter of the MC.Middle meningeal artery embolization

[0023] Embolization of the middle meningeal artery (MMA) has been used for the treatment of CSDH. MMA embolization is performed using small catheters including microcatheters through which liquid embolic agents (polymer agents; e.g. Onyx™) are injected to occlude the MMA and any new blood vessels (NBVs). When injected, theseembolic agents enter the MMA and reduce the overall vascularity of the meninges including the new blood vessels that have formed due to chronic inflammation.

[0024] Occlusion of the MMA and newly formed vessels stops the blood flow in these vessels and effectively reduces the risk of bleeding and thus CSDH formation and recurrence as shown in Figure 3.

[0025] Figure 3 shows a schematic middle meningeal artery (MMA) embolization procedure where (A) shows a chronic subdural hematoma (CSDH) and NBVs prior to treatment (NBVs may or may not be seen with angiographic imaging). That is, a CSDH, with MMA supplying the covering may have given rise to many newly formed, curvy vessels (NBVs) with weak vessel walls that recurrently bleed and gave rise to the CSDH. (B) shows a catheter 30 delivering an embolic agent (e.g., Onyx™) into the MMA and NBVs. This results in vessel occlusion and shrinkage / disappearing of the NBVs over the course of a few weeks. (C) shows a few weeks after the embolization where the NBVs have disappeared, and the MMA has reduced. As a result, the CSDH has shrunk, and recurrence risk is substantially decreased.

[0026] MMA embolization has several challenges:1) As shown in Figure 3A, the MMA has anastomoses with important vessels 30a supplying the eyes and other important structures in the head including cranial nerves. Thus, the catheter 30 has to be navigated past the branch points at which the MMA gives rise to vessels supplying these other important structures. Importantly, reflux of the embolic agent 30b into these important branches has to be avoided.2) As shown in Figure 3B, in order to prevent backflow, a “plug” of embolic agent material 30b is created. To do this, the surgeon will administerthe embolic agent in a manner such that a plug is formed around the catheter to “seal the catheter tip”. Forming this plug does require a little bit of backflow to wrap the embolic agent around the catheter tip. Also, forming the plug takes care and a relatively long time because a) the embolic agent material must be released slowly from the catheter and b) because it is viscous, it is slow flowing. Further, it takes a relatively long time (about 20 minutes) to harden and form a stable plug. Sometimes, a plug cannot be formed at all and / or the embolic agent continues to reflux instead of moving forward. This carries the risk of embolization of important MMA side branches (e.g. 30a; Figure 3A). Additionally, even if embolization of important side branches does not occur, it leads to inadequate penetration of the distal vasculature resulting in an incomplete treatment. Sincethe distal vasculature is still patent, over a period of time, it can continue to get blood supply to alternative pathways.3) As shown in Figure 3B, if a plug can successfully be formed, the catheter tip often sticks to the plug and cannot be removed. Therefore, detachable catheters have been utilized, whereby the catheter has a detachment point below the tip, enabling the proximal portion of the catheter to be detached from the tip and withdrawn with the tip staying in the vessel once the procedure is finished. There are key challenges with this procedure including a. the surgeon typically allows reflux up to the detachment point which may not always be doable depending on the anatomy and the point of origin of critical branches just proximal to the tip of the microcatheter and b. it still adds to procedure time as the surgeon has to slowly inject to allow a controlled reflux to allow for a sufficient formation of a plug that can subsequently push the liquid embolic forward.4) The MMA is very small and tortuous, and navigating a catheter in such a tiny vessel (often < 1.5 mm) is challenging.5) As noted above, the patients are often old and uncooperative and move a lot during the procedure, especially during prolonged procedures. Therefore, the procedure often has to be performed under general anesthesia, and the longer the anesthesia, the higher the risk of anesthesia-related side effects. Therefore, it is desirable to have the procedure as short as possible.6) Vasospasm can occur during these procedures where the arterial vessels contract to narrow the vessel thus preventing catheters to be advanced through these vessels. Vasospasm is more likely to occur in patients who are smokers.7) As shown in Figure 3C, vessel bifurcations B1 , B2 and / or tortuous sections present problems for distal advancement F of MCs over a microwire MW as the distal tip 11 may become stuck at the bifurcation junction 30 and / or against a vessel wall which can make further advancement impossible.

[0027] In other similar procedures in other areas of the body, in order to avoid back-flow or reflux, a catheter with a mounted balloon is often used. After positioning the catheter, the balloon in inflated to form a plug and force the liquid embolic agent forward. However, even the smallest balloon catheters are often not small enough to fit into a normal sized MMA which is common in most CSDH patients (i.e., one that is not supplying a fistula). Also balloon catheters are expensive.

[0028] In accordance with the disclosure, MMA catheters (referred to herein as MMA catheters or MMACs) 10 enabling access into the MMA vessel system are described thatprovide effective sealing against a vessel wall to prevent back-flow whilst remaining sufficiently flexible to be navigated within the MMA, past various bifurcations and through tortuous regions of those vessels and that can be removed after release of embolic agent. It is understood that the catheter systems described here are described in reference to procedures that are performed in the MMA; however, the catheter systems may also be used in other vessels.

[0029] In general, and as shown in Figures 4-6, an MMA catheter 10 has a soft, highly flexible expanded region 10a at or close to the catheter tip 10b that can seal against a vessel 12. The expanded region described herein is defined as a sealing system. The portion of the catheter 10 between the catheter tip 10a and sealing system 10a is the tip region 10c. The sealing system 10a has the primary function of providing a seal between the MMA catheter 10 and the vessel wall 12 to prevent significant back-flow of polymer agents administered through the catheter. As opposed to a catheter with a detachable tip, where the tip remains in the vessel and blocks access for future procedures, the MMA catheter described in the disclosure can be fully removed after the procedure, when it has been determined that there has been sufficient forward penetration of the embolic agent.

[0030] Furthermore, because it is not necessary to form a plug with the liquid embolic agent itself when using the MMA catheter 10, the procedure time can be substantially shortened, thus, complications due to patient movement can be reduced and general anesthesia may potentially be avoided. In various embodiments, the sealing system has the following properties:• defines an outer seal that can fully engage with an MMA vessel 12 to prevent back-flow of materials ejected from the tip of the MMA catheter.• When flexed within a tight vessel curve (often 120 degrees or more) is sufficiently expandable on an outer surface of the sealing system to enable the MMA catheter to flex around the tight vessel radius (Figure 5).• When flexed within a tight vessel curve (often 120 degrees or more) is sufficiently compressible on an inner surface of the sealing system to enable the MMA catheter to flex around the tight vessel radius (Figure 5).• The sealing system is fabricated from atraumatic materials to prevent injury to the vessel intima and / or minimize the risk of causing vasospasm. This can include incorporating hydrophilic coatings to at least the distal tip portions of an MMA catheter and to the sealing system and may extend more proximally along the main body of the MMA catheter. To accomplish these objectives of preventing injury and minimizing the risk of causing vasospasm, the sealingsystem has a softness that reduces friction while maintaining sealing and preventing embolizing agent reflux. It is understood by those skilled in the art that while the foregoing language is functional, objective definition of specific properties or parameters such as “softness that reduces friction while maintaining sealing”, “minimizing the risk of causing vasospasm”, and “preventing embolizing agent reflux” is challenging to quantify for systems operating within the human vasculature using specific numerical values. However, these properties or parameters provide objective definition of the required performance of the sealing system and provide defined boundaries to the scope of the appended claims as understood by one of ordinary skill in the art.• The sealing system is positioned close to the tip of the MMA catheter approximately 0-50 mm from the tip, and more preferably 0-15 mm and still more preferably 0-5 mm from the tip 10b.• The OD of the sealing system is 0.8-2 mm being sized in 0.1 mm increments on appropriately sized catheters enabling a surgeon to select an MMA catheter sized for a target vessel.• The outer diameter (OD) of the sealing system is approximately 1.5-2.5 times the OD of the catheter.• The sealing system may have a distally facing taper that facilitates forward movement of the sealing system within tight curves.• the sealing system is a forward-facing conical leaf or disk having a stiffness enabling proximal inversion as the catheter is distally advanced and distal inversion when the catheter is moved proximally. The conical leaf is made of very soft material (typically silicon based).• the sealing system may be provided with radio-opaque markers to facilitate positioning.

[0031] Various features of the MMA catheter include:• The OD of the MMA catheter is 0.33-1.0 mm.The MMA catheter has a proximal region 10e that is sufficiently long to extend to outside the body.The overall length A of the MMA catheter is approximately 150-160 cm.

[0032] As shown in Figures 4-6, different embodiments of the MMA catheter 10 are shown. Generally, the MMA catheter has a lumen 10e and sealing system 10a.

[0033] As shown in Figure 4, in one embodiment, the sealing system is a bulb 10f . The bulb may include one or more slits, slots or channels 10g (shown schematically in dotted lines) that enhance the ability of the bulb to navigate through a tight vessel as shown in Figure 5. Such slits, slots or channels may be circumferential 10g, longitudinal 10 j or helical 11 or other designs that provides the ability of the bulb to both expand and compress within a curve.

[0034] In one design, the bulb has a forward facing (distal) side of the bulb that may include a surface 10k that facilitates the deflection of the bulb around a curve to further minimize the risk of the bulb getting stuck within a tight curve. For example, the forwardfacing surface 10k may include a concave surface that provides a shallower engagement angle when the bulb first engages with a curved vessel.

[0035] As shown in Figure 4A, in one embodiment, the bulb may be provided with a series of circumferential grooves 10m formed in the outer surface of the bulb that provides space for compression and expansion of the bulb.

[0036] As shown in Figure 4B, in one embodiment, the bulb may be provided with one or more helical grooves 11 formed in the outer surface of the bulb that provides space for compression and expansion of the bulb.

[0037] As shown in Figures 4C and 4D the sealing system 10a may be truncated on its proximal side.

[0038] In Figure 5, the sealing system is shown in a tight curve where the bulb is shown compressed 16 on the inside portion of the curve and expanded 15 on the outside portion of the curve during this manoeuvre where individual sections 10h may be opened or compressed relative to other sections.

[0039] In Figure 6, the sealing system is shown as series of separated disks 10i that may be distributed along a section of the MMA catheter. Such disks may be substantially adjacent to one another and may be of variable diameter with respect to one another. In one embodiment, the most distal and proximal disks may be smaller than the middle disk(s). During advancement, the disks may fold down against one another as the MMA catheter is pushed forward around curves but expand again when beyond a curve. The disks 10i may be of different diameters and profiles as shown in Figure 6. For example, in Figure 6, the two most proximal disks are wider than they are thick whereas the distal most disk is narrower than it is wide.

[0040] Figures 6A-6C illustrate the sealing system as a soft conical leaf 14 that can flip between a proximal inversion 14a (Figure 6A) and a distal inversion 14b (Figure 6B). In this embodiment, as the catheter is being pushed forward, the conical leaf may be proximally inverted and when the MMA catheter is in place, it is pulled back to place it in the distal inversion as shown by the arrow and dotted lines in Figure 6B.

[0041] Furthermore, Figure 6C shows the effect of injecting polymer. Normally, as polymer is injected, it increases the pressure within the vessel which may cause a slight expansion of the vessel as shown by the arrows in Figure 6C. The increase in pressure may also cause the conical leaf 14b to flex proximally against the expanded vessel wall which may maintain sealing and minimize reflux of polymer.

[0042] Figure 7A shows a possible problem during the advancement of a catheter when particular vessel bifurcations and / or particularly tortuous sections are reached and the sealing system 10 becomes stuck at the bifurcation. Figures 7B-7C show another embodiment of the MMA catheter where the sealing system includes at least one proximally angled disk 20 configured to the MMA catheter body. In this embodiment, the angle of the disk facilitates easing the sealing system past the bifurcation by reducing the contact angle between the sealing system and the bifurcation. For example, Figure 7A shows a distal disk making contact with the bifurcation at a substantially 90-degree angle whereas Figure 7C shows a reduced contact angle.

[0043] The proximal taper may be 10-30 degrees as shown in Figure 7B.

[0044] Regardless of the particular style of sealing system, as described above, the sealing system is configured to the exterior of the MMA catheter. The sealing system may be configured to the exterior of the MMA catheter by various manufacturing techniques including being molded to the exterior of the catheter during casting of the catheter body or the sealing system may be produced as a separate component that would be positioned over the previously produced catheter and subsequently adhered / glued to the catheter body.

[0045] The MMA catheter including sections 10a and 10c and potentially an equivalent section proximal to section 10a may be less stiff that more proximal lengths of the catheter body and more specifically having sufficient stiffness to flex past bifurcations and / or tortuous sections. That is, the distal sections of the MMA catheter system may require support of a microwire to enable forward movement of the MMA catheter tip. The term “stiffness” is a difficult term to quantify within a range of values; however, functional language that illustrates the relative functional capabilities to different sections of the catheter isunderstood by those skilled in the art as an accurate definition of stiffness and particularly how stiffness can be subtly varied to achieve a functional objective.

[0046] In addition, the material of the sealing system is an atraumatic polymer (e.g. silicone) that is sufficiently soft to minimize the risk of inducing vasospasm yet with sufficient stiffness to provide a seal. The sealing system and MMA catheter body may include a hydrophilic coating.

[0047] The catheter may be incorporated into a kit having two or more catheters each having a sealing system with different diameters to enable the surgeon to select a catheter most appropriate for the patient’s vessels.

[0048] In use, the MMA catheter 10 is advanced over a wire that has been navigated to the MMA vessels. Upon positioning of the tip 10b (which may include radio-opaque markers), the wire is removed and the embolic / polymer agent may be delivered to the vessel as shown in Figures 6 and 6C. The sealing system prevents / minimizes back-flow of the polymer agent to the proximal side of the sealing system. Generally, during the procedure, the surgeon can determine the degree of forward penetration of the polymer agent due to the presence of radio-opaque particles in the polymer agent. When the surgeon is satisfied that forward penetration is sufficient, the MMA catheter can be removed without the formation of a plug around the catheter tip.

[0049] The MMA catheter is described above for use in the MMA vessels; however, it is understood that a similar system can be used in other small vessel procedures where the administration of polymer agents are required for treatment of similar conditions including brain and spinal arteriovenous fistula.

[0050] For this procedure, and for the purposes of description, an arteriovenous fistula is an abnormal connection between arteries (high flow high pressure vessels) and veins (low flow low pressure vessels). As an illustrative example, spinal veins normally drain blood from the spinal cord. If there is an abnormal connection between spinal arteries and veins, the pressure in the veins increases and flow reverses (abnormal backflow) - this results in blood congestion in the spinal cord and impedes the spinal cord function (for example, patients cannot walk any more and have disturbed bladder and bowel function). The abnormal veins also enlarge as a result and can be seen in the MRI.

[0051] The spinal cord congestion can be seen as an enlargement and hyperintense signal on the T2 weighted MRI.

[0052] Spinal arteriovenous fistulas can be cured by occluding the abnormal connection point between the spinal arteries and veins.

[0053] The problems are that a) spinal arteries are very small (1 mm in diameter or less) and have sharp curves, b) spinal arteries supplying the fistula have many important side branches and c) the veins supplying the fistulas form collateral pathways if not all collateral pathways supplying the fistula are casted out with embolic agent.

[0054] By accidentally embolizing side branches when embolic agent refluxes, the operator can cause tetraplegia, i.e., permanent paresis of the legs, arms, and even death due to paresis of the diaphragm / breathing muscles. The present disclosure as described herein can prevent such side effects by effectively sealing off the catheter tip, and at the same time small and flexible enough to fit into the tiny and highly curvy arteries of the spinal cord.

[0055] As such, the catheter of the present disclosure can help to permanently cure the fistula, because by sealing off the catheter tip, the embolic agent can be injected with higher pressure and therefore better penetrate into all collateral pathways supplying the fistula.

[0056] Similar situations can be seen in the brain for example, there can be a dural fistula in the floor of the anterior cranial fossa that is supplies by a branch of the ophthalmic artery (this artery also supplies the eye). To be able to cure the fistula, it is important to access the branch of the ophthalmic artery and inject the liquid embolic agent without any reflux so as to affect the supply to the eye.Stabilizer Catheter

[0057] As shown in Figures 8, 8A and 8B, in various embodiments, the MMAC is configured with a stabilizer catheter (SC) 8. The SC is a catheter that is sized to fit over the MMAC to provide additional stiffness to the MMAC as it is advanced from a GC and to otherwise enhance the ability of the surgeon to position the MMAC at a desired location such as the MMA as described below.

[0058] As an MMAC is advanced beyond the GC, as noted above, the MMAC must be navigated through various vessel junctions, namely from larger vessels into smaller vessels and through tortuous sections of vessels. The relative angles of vessels leading towards a junction, and the relative angles of the vessel past the junction may all contribute to the relative ease or difficulty of advancing the MMAC past that junction. Depending on the particulars of a vessel junction, the SC can provide necessary support to the MMAC and MW as the assembly is being pushed forward. For example, if a MW and the tip of an MMAC are initially navigated into a smaller vessel, the friction of the MMAC tip against the smaller vessel wall may cause a proximal section of the MMAC to prolapse into another vessel. To prevent this, after gaining initial access into the smaller vessel, the SC can be advanced over the MW and MMAC to provide stiffness to the proximal section of the MMAC such thatthe MW / MMAC do not prolapse. Importantly, given the tip of the MMAC, the MMAC cannot be inserted into an SC at the start of a procedure. Similarly, if the assembly is too stiff as the MMAC is advanced through a tortuous section, withdrawing the SC can enable the MMAC to be advanced by reducing the stiffness of the assembly for navigation through tortuous sections.

[0059] By way of specific example, in navigating towards the MMA, the MMA comes off the internal maxillary artery at a challenging angle which causes the MMAC to lose forward pushability and / or causing collapse / prolapse of the MMAC in the branches of the internal maxillary artery, commonly the superficial temporal artery.

[0060] Figure 8 shows the distal region D of an assembly of catheters used to access the MMA. The assembly includes a guide catheter (GC) 11 , SC 8, guide wire (GW) 13 and MMAC 10 having a distal tip with 3 proximally angled disks 20 (referred to as the MMAC tip). As shown, the MMAC tip may be slightly larger in diameter relative to the internal diameter of the SC. The SC is sized to fit within the GC and the GW is within the MMAC.

[0061] Generally, a typical procedure includes the following steps: a. Arterial access is obtained via a groin puncture or radial artery puncture. The guide catheter is placed in the external carotid artery using standard approach with the use of a diagnostic catheter and wire. b. An assembly of the guide wire (GW), MMAC, and SC is advanced through the GC. The GC provides support to the smaller components as the assembly is advanced. c. The GC is held in place and the MW, SC and MMAC are progressively advanced to the MMA. Typically, each of the MW, MMAC are selectively advanced to gain access to the desired vessel whilst the SC is providing support to the assembly as a whole. d. Once the desired location is reached, liquid embolic agent is injected into the MMAC. e. The MMAC and SC are withdrawn into the GC and the assembly is withdrawn from the body.

[0062] Importantly, the SC provides selective stiffness and flexibility to the MMAC to enable it to be advanced across / through various vessel junctions and / or through tortuous vessels. That is, through selective movement of the MW, MMAC and SC, the MMAC can be advanced through the vessels north of the GC. In particular, as described above, as the assembly is advanced and vessels narrow, the friction of the MMAC contacting the vesselwall 12 can cause an unsupported MMAC to collapse and / or prolapse which can prevent further advance. As such, the SC can be manipulated over the MMAC to provide selective stiffness to the MMAC allowing it to be advanced.

[0063] Figure 8A shows a proximal region P of the assembly and the components that are manipulated by a physician during the procedure.

[0064] Generally, all catheters such as GCs, microcatheters and other catheters are configured with standard proximal end fittings 15 that can be connected to various components such as rotating hemostatic valves (RHVs) 18. As is known, a typical RHV has a distal end fitting 18a configured to connect to a proximal end fitting 15 of a catheter. RHVs are also configured to enable an assembly of catheters to pass through the RHV and to enable fluids to be introduced into the catheter assembly. Atypical RHV has rotating sleeve that can be rotated to compress a catheter to restrict the flow of fluids through the catheter.

[0065] Typically, in preparing for a procedure and conducting the procedure, the physician will assemble catheters required for a procedure by inserting catheters into one another. That is, starting with the largest catheter, such as a GO, the GO is attached to an RHV via its proximal connector 15. The next smallest catheter is inserted into the proximal end of the larger catheter through the RHV. When a smaller catheter has been pushed through the larger catheter, a further RHV may be connected and the process repeated as necessary to build up a tri- or quadra-axial assembly of catheters. One or more wires may also form part of the assembly.

[0066] Once assembled, the distal end of the assembly is introduced into a vessel and the procedure is undertaken. During the procedure, the physician selectively manipulates each of the connectors 15 and RHVs by linearly pushing and pulling each relative to each other such that the distal tips of each slide relative to each other.

[0067] In one embodiment, a pre-manufactured assembly of an MMAC 10 and SC 8 is described as shown in Figure 8B. It should be noted that the dimensions shown in Figure 8B are not necessarily to scale and, in particular, the relative distances between components as denoted by the braces E, F, G may be varied. Importantly, as described, the MMAC tip prevents insertion of the MMAC through a SC at the proximal end of the SC. Further, as the MMAC is configured with standard proximal end fittings, insertion from the distal end is not possible. Accordingly, an MMAC / SC assembly is pre-manufactured such that the proximal end fittings are attached to the MMAC after the MMAC and SC have been assembled.

[0068] The following general manufacturing steps may be conducted:a. The MMAC body is manufactured with a sealing system at the MMAC body distal end. b. The SC body is manufactured with a proximal end fitting. c. The proximal end of the MMAC is inserted into the distal end of the SC and pushed back to extend from the proximal end of the SC and, optionally, through a connected RHV 18. d. A proximal end fitting is connected to the proximal end of the MMAC. e. Alternatively, an MC without the anti-reflux tip is inserted into the combination of SC and RHV from the proximal end and then the anti-reflux tip in constructed at the distal end of the MC f. The assembly is packaged.

[0069] In various embodiments, as shown in Figure 8B, a second RHV 18’ may be configured to the assembly. RHV 18’ would be used during the procedure to connect a GC to the assembly. If configured, at the time of the procedure, the physician would select the desired GC and insert the distal end of the assembly into the proximal end of the GC and when pushed through, connect the proximal end fitting of the GC to the RHV 18’. The inclusion of RHV 18’ as part of the pre-manufactured assembly is optional.

[0070] In another embodiment, in order to prevent inadvertent movement of the MMAC tip proximally into or against the distal tip of the SC, the assembly is provided with a stopper system that limits proximal movement of the MMAC relative to the SC.

[0071] As shown schematically in Figure 8C, the outer surface of the MMAC catheter 10 is provided with a first stopper 10a and an inner surface of the RHV is provided with a second stopper 18a that collectively provide limits to the linear movement of the MMAC relative to the SC. Position A shows the position where the MMAC tip is furthest from the distal tip of the SC and position B shows the position where the MMAC tip is closest to the distal tip of the SC where the proximal end fitting 15 of the MMAC is pulled back relative to the RHV 18 which is connected to the SC 8. Stoppers 10a and 18a are not engaged in position A but are engaged in position B which limits the proximal movement of the MMAC relative to the SC. The stoppers are preferably circumferential to enable the MMAC and SC to be torqued relative to one another. That is, stopper 10a may be a circumferential disk and stopper 18a may be a circumferential surface that engages with stopper 10a.

[0072] In this embodiment, the manufacturing steps will require that the MMAC stopper 10a is configured to the MMAC prior to configuring the proximal end fitting 15.

[0073] Figure 8D shows an alternative embodiment of the stopper system where stoppers 10a and 18a are configured distal to an RHV. In this embodiment the outer surface of the MMAC catheter 10 is provided with a first stopper 10a and an inner surface of the SC 8 is provided with a second stopper 18a that collectively provide limits to the linear movement of the MMAC relative to the SC. As above, position A shows the position where the MMAC tip is furthest from the distal tip of the SC and position B shows the position where the MMAC tip is closest to the distal tip of the SC where the proximal end fitting 15 of the MMAC is pulled back relative to the RHV 18 which is connected to the SC 8. Stoppers 10a and 18a are not engaged in position A but are engaged in position B which limits the proximal movement of the MMAC relative to the SC. The stoppers are preferably circumferential to enable the MMAC and SC to be torqued relative to one another. That is, stopper 10a may be a circumferential disk and stopper 18a may be a circumferential surface that engages with stopper 10a.

[0074] In this embodiment, the manufacturing steps will require that the SC 8 is configured with stopper 18a, the MMAC is configured with stopper 10a and the SC and MMAC are assembled within an RHV prior to configuring the proximal end fitting 15.

[0075] It is understood that the steps outlined above are representative and that manufacturing could be completed in different orders. For example, both MMAC and SC bodies could be manufactured with their respective end fittings, assembled wherein the distal end of the MMAC body is inserted into the proximal end of the SC and the sealing system attached to the MMAC body thereafter.

[0076] Other features of the assembly will typically include:• The outer diameter of the SC is not higher than the MMAC tip such that the SC will go through the same size GC• The MMAC is longer than the SC and the SC is longer than the GC with sufficient differences in length to enable significant linear displacement of each relative to one another.• Typical lengths: o GC: 90-100 cm o SC: 110-125 cm o MMAC: 145-165 cm

[0077] In a typical case in gaining access to the MMA, the distal end of the GC would be placed in the internal maxillary artery, the distal end of the SC would be placed at the origin of the MMA or in certain situation could be advanced into the proximal MMA and the MMAC would be positioned more distally in the MMA such that it is safe for embolization.Experimental

[0078] Three randomized controlled trials were performed that compared middle meningeal artery embolization (MMAE) in addition to standard of care vs. standard of care in patients with non-acute subdural hematoma (SDH). All three trials showed a significant benefit of MMAE compared to standard of care with no increase in complications.

[0079] The MAGIC-MT trial was conducted in China and randomized 727 patients to either best medical care, which included medical management and / or surgical treatment, or MMAE with Onyx in addition to best medical care. The primary endpoint, which was any death, symptomatic SDH progression or recurrence, was seen in 7.2% in the MMAE arm vs. 12.2% in the control arm, corresponding to an odds ratio of -4.93 (95%confidence interval -9.37 - 0.063).

[0080] Serious adverse events were significantly less common in the MMAE arm (6.7%) vs. the control arm (11.6%), p=0.02.

[0081] The STEM trial was conducted in the US and randomized 310 patients with non- acute SDH to either MMAE using SQUID™ in addition to standard of care or standard of care alone. The primary endpoint, which was residual / recurrent SDH or any new major disabling stroke, myocardial infarction or death from any neurological cause, was observed in 15.2% in the MMAE arm and 39.2% in the control arm, suggesting a significant benefit of MMAE with an odds ratio of 3.60 (95% confidence interval 1 .91 - 6.78).

[0082] The EMBOLISE trial was conducted in the US and randomized 400 patients to either best medical care, or MMAE with Onyx in addition to best medical care. The primary endpoint, which was SDH recurrence / progression requiring surgical drainage, occurred in 4.1% in the MMAE arm and 11.3% in the control arm, suggesting a significant benefit of MMAE with a relative risk of 0.36 (95% confidence interval 0.11-0.80).

Claims

CLAIMS1. An assembly comprising: a microcatheter (MC) body having a distal catheter tip, the microcatheter body configured with an anti-reflux sealing system adjacent a microcatheter tip, configured to enable contact with a vessel wall to effect sealing of distal fluids from proximal fluids on opposite sides of the sealing system and wherein the sealing system has sufficient compressibility to enable flexure of the sealing system around a tight bend of a patient’s vasculature and to enable passage of an embolizing agent through the microcatheter body from the distal microcatheter tip, the sealing system having a sealing system outer diameter and the microcatheter body having an MC proximal connector; and, a stabilizer catheter (SC) having a SC proximal connector, the SC preconfigured over the microcatheter body between the sealing system and MC proximal connector, the SC having an outer diameter equal to or less than the sealing system outer diameter.

2. The assembly of claim 1 further comprising a valve configured to the assembly between the SC proximal connector and the MC proximal connector and wherein the valve is configured to connect to the SC proximal connector.

3. The assembly of claim 1 or claim 2 further comprising a second valve configured to the assembly over the SC and distal to the SC proximal connector.

4. The assembly of any one of claims 1-3 wherein the SC is 110-125 cm and the MMAC is 145-165 cm.

5. The assembly of any one of claims 2-4 wherein the MC body includes a first stopper configured to an outer surface of the MC body and the valve is configured with a second stopper and where the first and second stoppers are engageable to limit proximal movement of the MC body relative to the SC.

6. The assembly of any one of claims 2-4 wherein the MC body includes a first stopper configured to an outer surface of the MC body and the SC includes a second stopper configured to an inner surface of the SC and where the first and second stoppers are engageable to limit proximal movement of the MC body relative to the SC.

7. The assembly as in claim 5 or claim 6 wherein the first and second stoppers are configured to prevent the sealing system from engaging with a distal tip of the SC.

8. The assembly as in any one of claims 5-7 wherein the first stopper is a circumferential disk.

9. A method of manufacturing a microcatheter assembly as in claim 1 comprising the steps of: forming a MMAC body having a sealing system on a distal tip of the MMAC body and a MMAC proximal end fitting; forming an SC body with a SC proximal end fitting; wherein the MMAC body is configured within the SC body, and wherein the SC body and SC proximal end fitting are configured between the MMAC proximal end fitting and sealing system; and, packaging the assembly.

10. The method as in claim 9 wherein the method further comprises the step of configuring a valve over the MMAC body distally to the proximal end of the MMAC body.11 . The method as in claim 10 further comprising the step of configuring a second valve over the SC body distally to the SC end fitting.

12. The method as in any one of claims 10-11 further comprising the step of forming a stopper system on the MMAC body and valve.

13. A microcatheter comprising: a microcatheter body having a distal catheter tip for placement within a middle meningeal artery (MMA), the catheter body configured with an anti-reflux sealing system adjacent a microcatheter tip, the sealing system being non-inflatable and configured to enable contact with an MMA vessel wall to effect sealing of distal fluids from proximal fluids on opposite sides of the sealing system and wherein the sealing system has sufficient compressibility to enable flexure of the sealing system around a tight bend of a patient’s vasculature and to enable passage of an embolizing agent through the microcatheter body and from the distal microcatheter tip.

14. The microcatheter of claim 13 wherein the sealing system includes at least one proximally angled disk.

15. The microcatheter as in claim 14 where the sealing system has an outer diameter of 0.8-2 mm.

16. The microcatheter as in claim 14 where the microcatheter body has an outer diameter of 0.5-1.0 mm.

17. The microcatheter as in any one of claims 13-16 wherein the sealing system is 0-50 mm from the distal microcatheter tip.

18. The microcatheter as in claim 17 wherein the sealing system is 0-5 mm from the distal microcatheter tip.

19. The microcatheter as in any one of claims 16-18 wherein the outer diameter of the sealing system is 1.5-2.5 times the OD of the microcatheter body.

20. The microcatheter as in any one of claims 13-19 having a radio-opaque marker.

21. The microcatheter as in any one of claims 13-20 wherein the sealing system has a softness to minimize vasospasm when contacting a vessel wall.

22. The microcatheter as in any one of claims 13-21 wherein the microcatheter has a proximal microcatheter section between the sealing system and a proximal end of the microcatheter and distal microcatheter section distal to the proximal microcatheter section and the distal microcatheter section is configured with a distal stiffness less than a proximal microcatheter section stiffness and wherein the distal stiffness facilitates movement of the distal microcatheter section past an MMA bifurcation or MMA tortuous section.

23. A kit comprising at least two MMA microcatheters of claim 13 wherein each MMA catheter has a sealing system having a different outside diameter.

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